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Table 17.4 Clinical Manifestations of Hypothyroidism



Organ System







Puffy appearance, dry, course, yellow-tinted skin brittle nails,



wound healing slowed, hair loss


Enlarged heart, changes in electrocardiographs


Maximal breathing capacity reduced, obstructive sleep apnea,



fluid accumulation in the pleural cavity


Reduced appetite with modest weight gain



Stiffness, aching



Slowing of intellectual functions, lethargy, headaches




described in Table 17.4, and individual effects may be misdiagnosed as organ-specific toxicity. Hypothyroidism can result from various causes other than chemical toxicity including diseases of the hypothalamic–pituitary–thyroidal axis, iodine deficiency, and heritable defects in thyroid hormone production. Chemical agents that have historically been recognized for their ability to cause hypothyroidism include phenylbutazone, resorcinol, lithium, and para-aminosalicylic acid.

Disruptions in thyroid hormone levels can occur through chemical-induced increases in the metabolic inactivation and elimination of the hormone. Chemicals that are capable of increasing the metabolic clearance of thyroid hormone include the polycyclic halogenated hydrocarbons (i.e., dioxins, furans, polychlorinated biphenyls, polybrominated biphenyls). A study reported in the New England Journal of Medicine suggested that environmental or occupational exposure to such chemicals can result in hypothyroidism in humans. The study consisted of a comparison of thyroid status in workers who were occupationally exposed to polybrominated biphenyls as compared to workers who were not exposed to any polyhalogenated hydrocarbons. Four of 35 exposed workers and none of 89 unexposed workers exhibited signs of hypothyroidism that included increased plasma levels of thyrotropin and decreased plasma levels of thyroxine. Thyrotropin is secreted by the pituitary gland and stimulates the thyroid gland to produce thyroxine (see Figure 17.1). The increase in thyrotropin and decrease in thyroxine is consistent with hypothyroidism caused by increased clearance of the thyroxine. As discussed earlier in this chapter, perinatal exposure to PBBs during the Michigan milk contamination also produced symptoms characteristics of hypothyroidism.


The endocrine system possesses many targets at which toxicants can elicit either reversible or permanent effects on an individual. Effects of chemicals on endocrineregulated processes such as development, maturation, growth, and reproduction have been well documented in both laboratory and epidemiological studies. Less is know of the potential effects of endocrine toxicants on more generalized endocrine-regulated processes such as bone maintenance, general organ function, and metabolism. The US Environmental Protection Agency has been mandated by the US Congress to develop and implement a program for the screening and testing of chemicals for endocrinedisrupting toxicity. At this writing, the EPA is in the process of developing such a



program that will focus on the effects of chemicals on the androgen/estrogen and thyroid hormone regulated processes. Once implemented, this required testing will greatly expand our knowledge of the extent to which humans are exposed to chemicals that interfere with processes regulated by these hormones. However, it is important to recognize that chemicals have the potential ability to interfere with other hormone cascades, including those involving mineralcorticoids, glucocorticoids, retinoids, and perhaps some peptide hormones. Research is needed to increase our understanding of the susceptibility of endocrine signaling pathways involving these hormones to chemical toxicity and, ultimately, to our establishing chemical exposure limits that include these considerations.


Bahn, A. K., J. L. Mills, P. J. Snyder, et al. Hypothyroidism in workers exposed to polybrominated biphenyls. N. Engl. J. Med. 302: 31–33, 1980.

Beas, F., L. Vargas, R. P. Spada, and N. Merchack. Pseudoprecocious puberty in infants caused by dermal ointment containing estrogens. J. Pediatr. 75: 127–130, 1962.

Blanck, H. M., M. Marcus, P. E. Tolbert, C. Rubin, A. K. Henderson, V. S. Hertzberg, R. H. Zhang, and L. Cameron. Age at menarche and tanner stage in girls exposed in utero and postnatally to polybrominated biphenyls. Epidemiology 11: 641–647, 2000.

Colborn, T., and C. Clement, eds. Chemically-induced alterations in sexual and functional development: The Wildlife/Human Connection. In Advances in Modern Environmental Toxicology, M. A. Mehlman, ed. Princeton, NJ: Princeton Scientific Publishing, 1992.

DiRaimondo, C. V., A. L. Roach, and C. K. Meador. Gynecomastia from exposure to vagina estrogen cream. N. Engl. J. Med. 302: 1089–1090, 1980.

Greenspan, F. S., and G. J. Strewler, eds. Basic and Clinical Endocrinology. Stamford, CT: Appleton and Lange, 1997.

Guillette, L, Jr. and D. A. Crain, eds. Environmental endocrine disrupters. New York: Taylor and Francis, 2000.

McLachlan, J. A. Environmental signaling: What embryos and evolution teach us about endocrine disrupting chemicals. Endocrine Rev. 22: 319–341, 2001.

Wilson, J. D., and D. W. Foster, eds. Textbook of Endocrinology. Philadelphia: Saunders, 1992.